As an undergraduate student, Moe Mahjoub’s research findings on a gene involved in microtubule severing were published in the Journal of Cell Science, listing him as first author. Microtubules are thin tubes of protein and an essential element of the cell skeleton required for cell division and movement. Moe’s current research is directed at understanding how microtubule severing is regulated, using unicellular algae called Chlamydomonas. Microtubule severing is key to the algae’s shedding of flagella, or whip-like appendages, in response to a wide array of stimuli. This process has important implications for human health. For example, sterility can result when sperm shed flagella in response to ingested toxins. This research could help explain a range of diseases, including retinal degeneration, kidney disease and cancer.
Research Pillar: Biomedical
Tracking the B-cell repertoire associated with the broadly-neutralizing antibody response in HIV-1 infection
The progression from HIV infection to AIDS occurs because the body’s immune system fails to control replication of the virus. While broadly neutralizing antibodies (bNtAb) are unable to clear an established infection, they have shown promise in providing protection against the contraction of HIV. However bNtAb have proven to be extremely difficult to generate by immunization. Marinieve Montero is studying the antigenicity and immunogenicity of the HIV-1 transmenbrane glycoprotein gp41, to which several bNtAb are directed. Her work will involve an exhaustive biochemical characterization of the gp41 protein presentation in the context of membranes, and the analysis of the bNtAb response generated after immunization of animals. The results from her study will improve the understanding of the biology of bNtAb production, and may be a valuable aid in the design of successful vaccine candidates and immunization methods.
Molecular dissection of neural stem cells
Damage to the central nervous system caused by conditions such as Alzheimer’s disease, Parkinson’s disease, stroke and spinal cord injuries was once considered irreversible. But recent scientific advances suggest neural stem cells may hold the key to restoring the damaged area of the brain, giving hope to people suffering from these devastating conditions. Scientists have discovered that transplanted neural stem cells have the ability to reproduce themselves and become mature cells capable of performing nervous system functions. However, isolating these cells has proven difficult since researchers have yet to find markers that identify neural stem cells. Barbara Murdoch is working to identify proteins specific to the surface of neural stem cells so she can study their growth requirements. By solving this puzzle, scientists will be able to more effectively use neural stem cells for therapies that promote nervous system recovery.
The role of intraepithelial lymphocytes in cutaneous immunity and in the generation of psoriasiform pathology
Seborrheic dermatitis and psoriasis are chronic, inflammatory skin conditions that are extremely difficult to treat. Despite extensive research, the cause of these conditions is not known, although they have been linked to impairment of normal immunological response. Darryl Oble is investigating whether a genetic defect that renders cells unable to signal the immune system to repair damage predisposes people to developing inflammatory skin conditions. Similar genetic issues are involved in other immunologically-based diseases, such as Type 1 diabetes, inflammatory bowel disease, cancer and other conditions. As a result, this research could help explain how these diseases develop, lead to more successful treatments for a variety of conditions and reduce side effects.
Agonist-specific Ca2+ signalling micro-domains in vascular smooth muscle cytoplasm and mitochondria
Building on his earlier research, which was supported by a MSFHR Trainee Award, Damon Poburko is now investigating the mechanisms involved in mitochondrial regulation of calcium. An average cell has several hundred mitochondria, which provide the energy for cells to function properly. Research has shown mitochondria are involved in programmed cell death, or apoptosis, when they take up large, toxic loads of calcium. In addition, mitochondria sense calcium changes, allowing them to tailor energy production to cell needs. Mitochondria also help regulate intracellular calcium levels, which determine blood vessel constriction in vascular muscle. The findings should help explain how vascular tone is regulated, and how blood is shunted to different parts of the body as needed. Ultimately, this research may lead to the development of new therapies to treat vascular diseases.
Anoxia and the regulation of intracellular ion concentrations in hippocampal neurons
Neurons (nerve cells) need a regular supply of oxygen and nutrients to survive. When neurons are deprived of these essential factors for more than a few minutes, such as during a stroke or cardiac arrest, they undergo changes that lead to cell death. Intracellular concentrations of ions (e.g. sodium ions, calcium ions and protons) show dramatic changes during and following periods of anoxia or ischemia (oxygen deprivation). These changes play an important role in determining subsequent neuronal damage or death. Claire Sheldon is characterizing these anoxia-evoked changes in sodium ions, calcium ions and protons in hippocampal neurons and hopes to identify the mechanisms which contribute to their production. Her research focuses on the role(s) of intracellular pH regulating mechanisms to the changes observed, with particular emphasis on the Na+/H+ exchanger, an acid-extruding mechanism present in hippocampal neurons. Claire hopes her research will lead to new strategies to prevent or limit neuron death and the debilitating effects that stroke or cardiac arrest have on the central nervous system.
Characterization of a YAC mouse model of Huntington disease for use in therapeutic trials
Huntington disease (HD) is an inherited, neurodegenerative disease characterized by loss of motor control and cognitive decline, eventually leading to death. Elizabeth Slow is studying atrophy and cell loss in the striatum, the most affected region of the brain, and the motor dysfunction associated with HD. A group of proteins called caspases split other proteins, including huntingtin, the protein produced by the HD gene. In collaboration with researchers at Harvard, the University of California and the Buck Institute in California, Elizabeth is investigating whether this process triggers inappropriate cell suicide in the neurons affected by HD, thus causing the disease. If so, the results will determine whether caspase inhibitors are an effective treatment option for people with Huntington disease, which currently has no treatments to prevent or delay the condition.
Model Membrane studies of Amphotericin B's mechanism of action (towards less toxic AmB formulations and new tools for drug/membrane studies)
Amphotericin B (AmB) is an antifungal antibiotic used to treat infections in patients with depressed immune systems, such as cancer patients, organ donor recipients, diabetics and people with AIDS. Fungal infections are thought to account for up to 30 per cent of deaths among these patients. Although effective, use of AmB is limited because it can also cause kidney toxicity. AmB is known to interact with parts of the cell membrane, forming pores that allow leakage and ultimately cause cell death, but this process is poorly understood. Robin Stoodley is researching how the drug interacts with the body at the cellular and molecular levels, with the goal of finding ways to reformulate AmB to reduce its toxicity and improve effectiveness. The techniques Robin develops for this research may also be used to study chemotherapy and other drugs, leading to the development of better drug therapies.
Pathogenesis of confined placental mosaicism (CMP) during pregnancy
The frequency of chromosomal abnormalities in reproduction is significant — 15 to 20 per cent of all pregnancies end in spontaneous abortion, and half of these miscarriages are associated with chromosomal abnormalities. In 1983, two UBC professors discovered a condition now known as confined placental mosaicism (CPM), where a chromosomal abnormality is present in the placenta but not the fetus. CPM allows a pregnancy that would otherwise spontaneously abort to continue to term, and is present in at least two per cent of pregnancies. In his earlier research, Paul Yong confirmed that some types of CPM increase the risk for poor fetal outcomes such as low birth weight or complications such as pre-eclampsia. Now he is studying how chromosomal abnormalities cause alterations in placental structure and function. The hope is to identify potential therapeutic interventions in pregnancies affected by chromosome abnormalities in the placenta.
Development of a direct computer interface using descending motor potentials recorded from the spinal cord
A variety of devices are available for individuals with motor impairments, such as electrical stimulation systems for locomotion. But people with severe disabilities are often unable to control these devices effectively. Dr. Jaimie Borisoff, who has published research papers on neural regeneration in the journals Experimental Neurology and Molecular and Cellular Neuroscience, is researching assistive technologies to enhance quality of life for people with severe disabilities. Jaimie is investigating whether motor control information can be recorded directly from the spinal cord, since much of the intentional and logistical processing has already been performed in the brain before the signal pathway terminates at the spinal lesion. If so, this information could be used to create a control system that uses signals from the spinal cord.